PGSS

Particle formation from gas saturated solutions (PGSS), 24 17, 18 Particle formation, supercritical fluids in, 24 17-19... 

The systems which are often involved in RESS and also in PGSS are highly asymmetrical binary mixtures which contain two substances with large differences in molecular size, structure, and intermolecular interactions. Two main features of the phase-behaviours for such systems are ... 

In a relatively new process for production and fractionation of fine particles by the use of compressible media - the PGSS process (Particles from Gas-Saturated Solutions) - the compressible medium is solubilized in the substance which has to be micronized [58-61]. Then the gas-containing solution is rapidly expanded in an expansion unit (e.g., a nozzle) and the gas is evaporated. Owing to the Joule-Thomson effect and/or the evaporation and the volume-expansion of the gas, the solution cools down below the solidification temperature of the solute, and fine particles are formed. The solute is separated and fractionated from the gas stream by a cyclone and electro-filter. The PGSS process was tested in the pilot- and technical size on various classes of substances (polymers, resins, waxes, surface-active components, and pharmaceuticals). The powders produced show narrow particle-size distributions, and have improved properties compared to the conventional produced powders. 

The Joule-Thomson coefficient is the slope of the isenthalpic lines in the P-T projection. In the region where iJt<0, expansion through the valve (a decrease in pressure) results in an increase in temperature, whereas in the region where pJt >0, expansion results in a reduction in temperature. The latter area is recommendable for applying the PGSS process. 

In PGSS, knowledge of the P-T trace of the S-L-V equilibrium gives information on the pressure needed to melt the substance to be micronized and form a liquid phase at a given temperature, and to calculate its composition. 

In general, a system with a negative dP/dT slope and/or with a temperature-minimum in the S-L-V curve could be processed by PGSS. 

Figure 9.8-6. Basic scheme of experimental equipment for PGSS.

One goal of RESS/CSS, the anti-solvent processes such GAS, and the PGSS process, is to obtain submicron- or micron-sized particles. Technological features of the various high-pressure micronization processes are summarised and compared in Table 9.8-4 [58]. 

Restrictions arising from the difficult product- and gas-recovery in the RESS and GASR, GASP, SAS/PCA/SEDS processes are avoided by the PGSS process. 

The PGSS process has several advantages which favour its use for large scale applications. This process has promise for the processing of low-melting, highly viscous, waxy, and sticky compounds, even if the obtained particles are not of submicron size. The process already runs in plants with a capacity of some hundred kilograms per hour. 

Technological features of RESS, GASR and PGSS process... 

Up to the present time the application of the PGSS process has been investigated for following products ... 

Figure 9.8-10. Influence of the pre-expan- Figure 9.8-11. View of monoglyceride sion pressure on the bulk density. particle processed by PGSS.

Based on phase-equilibrium data in the Master diagram (Figure 9.8-12) (where S-l and 1-V equilibrium data are presented) the experiments for cocoa butter micronization using the PGSS process were carried out. The pre-expansion pressure was in the range of 60 to 200 bar and at temperatures from 20 to 80°C. The micronization with the nozzle D = 0.25 mm resulted in fine solid particles with median particle sizes of about 62 pm. In Figure 9.8-13 the morphology of a cocoa-butter particle is presented. 

From DSC measurements it was deduced that the crystallinity of a freshly micronized sample is about 80% and that it crystallizes in the stable polymorphic form P2. Under the operating conditions mentioned, the PGSS process caused no degradation of cocoa butter and the product was a powder with a narrow and very controllable size-distribution. 

The practically water-insoluble compounds nifedipine and felodipine, which are dihydropyridine calcium-channel-blockers were processed by the PGSS process with the aim of increasing their dissolution rate and hence bioavailability [71,72]. 

Using the PGSS process, nifedipine was micronized at various pressures in the range from 100 to 200 bar and at temperatures 165, 175 and 185°C. The mean particle-size of the starting... 

The mean particle size of the starting felodipine was 60 pm, and reduced after micronization with the PGSS process to 42 pm. Specific surface areas measured using the BET method increased from 0.33 m2/g for the starting felodipine to 1.33 m2/g for micronized felodipine. 

The dissolution profiles of PGSS-felodipine/PEG 4000 co-precipitates, along with starting felodipine and its physical mixture with PEG 4000 (1 4), are presented in Figure 9.8-15. The amount of felodipine dissolved in 1 h from felodipine/PEG 4000 co-precipitates micronized at pre-expansion pressures of 175, 190 and 195 bar is 13.5-, 10-, and 8-times higher than that of original felodipine. 

With the PGSS process, micronized drugs and drug/PEG 4000 samples were prepared in a new way, which has some advantages over conventional methods for the micronization of pure drugs and for drug/carrier solid dispersion preparation, namely fusion methods and solvent processes. 

Figure 9.8.17. Shape of the particles of PEG obtained by the PGSS process.

The experiments on the PGSS of PEG were performed in a laboratory-scale plant with sample sizes of about 200-400 g powder, and in a small pilot plant with sample sizes of 1-3 kg powder. Depending on the nozzles (orifices 0.4 / 0.5 /1.0 mm, spraying angles 30° and 90°), the kind of PEG (MW 1500/4000/8000/35000) and on pressure (100-250 bar) and temperature (45-70°C) three classes of particles were obtained fibres, spheres and sponges as presented in Figure 9.8-17. 

The advantages of the PGSS process over conventional methods of particle-size reduction are numerous. 

Through the choice of the appropriate combination of solvent and operating conditions for a particular compound, PGSS can eliminate some of the disadvantages of traditional methods of particle-size redistribution in material processing. Solids formation by PGSS therefore shows potential for the production of crystalline and amorphous powders with a narrow and controllable size-distribution, thin films, and mixtures of amorphous materials. 

Although most of the applications of supercritical particle formation are known in the pharmaceutical industry, some examples can be found with foodstuff. Cocoa butter a relatively high value product has been successfully micronised using the PGSS (particles from gas-saturated solutions) process [4], In this paper we will investigate the production of fine cocoa butter crystals in order to use them for the seeding of chocolate. 

A new developed process PGSS (Particles from Gas Saturated Solutions) was applied for generation of powder from polyethyleneglycols. Principle of PGSS process is described and phase equilibrium data for the binary systems PEG-CO2 for the vapour-liquid and the solid-liquid range are presented in a master diagram . The influence of the process parameters on particle size, particle size distribution, shape, bulk density and crystallinity is discussed. 

Several new processes for formation of solid particles with defined particle size and particle size distribution using supercritical fluids were developed in the past years. Examples are crystallisation from supercritical fluids, rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallisation (GASR), and PGSS (Particles from Gas Saturated Solutions)-process [1,2]. 

For the design of a process for formation of solid particles using supercritical fluids, data on solid - liquid and vapour - liquid phase equilibrium are essential. PGSS process is only possible for systems where enough gas is solubilized in the liquid. 

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